Overview of complications of severe burn injury

INTRODUCTION — Despite major advances in the treatment of patients with burn injury, systemic complications and burn wound-specific complications are common [1-3].

The definition of a severe burn injury (table 1) and the treatment of burn wounds are reviewed separately. (See "Overview of the management of the severely burned patient" and "Treatment of superficial burns requiring hospital admission" and "Treatment of deep burns".)

SYSTEMIC COMPLICATIONS

Multisystem organ dysfunction — Multiple organ dysfunction syndrome (MODS) is a progressive disorder that commonly occurs in acutely ill patients, regardless of etiology of the injury or illness. MODS exists in a continuum with the systemic inflammatory response syndrome (SIRS) which affects most patients with a severe burn, with or without an infection [1,4]. The risk of MODS increases with burn wounds >20 percent total body surface area (TBSA), increasing age, male sex, sepsis, hypoperfusion, and under-resuscitation [5-7]. Approximately 50 percent of patients who succumbed to the burn injury had been diagnosed with MODS [6]. Most patients with MODS have an inability to attenuate the inflammatory response to injury. (See "Sepsis syndromes in adults: Epidemiology, definitions, clinical presentation, diagnosis, and prognosis", section on 'Multiple organ dysfunction syndrome' and "Sepsis syndromes in adults: Epidemiology, definitions, clinical presentation, diagnosis, and prognosis", section on 'Definitions'.)

In general, the burn wound or lungs are the most likely sites for an infection in the severely burned patient that subsequently develops MODS [1]. The release of endotoxins and/or exotoxins from an infective process initiates a cascade of inflammatory mediators that leads to organ damage and ultimately organ failure. Targeting the different cascade systems involved in the pathogenesis of burn-induced MODS is often not a feasible option [8]. Prevention of sepsis from burn wound infection is the most promising approach, as illustrated by the following examples:

●Wound-associated inflammation is limited by immediate debridement of devitalized tissue and tangential excision of burn tissue and wound closure, primarily by skin grafts, within 48 hours of a full-thickness burn [1,9-14]. (See "Hypermetabolic response to moderate-to-severe burn injury and management", section on 'Early excision and grafting' and "Burn wound infection and sepsis".)

●Patients should be weaned from the ventilator and ambulated as soon as clinically feasible to minimize the risk of pulmonary complications.

●Early enteral nutrition in severely burned patients is associated with decreased bacterial translocation and aids in attenuating the immune response post-injury [15].

Severely burned patients develop MODS primarily at two different distinct points: early, due to hypoperfusion and under-resuscitation, or late, due to sepsis. In general, MODS begins in the renal or pulmonary system, and progresses systematically to the liver, gastrointestinal system, hematologic system, and central nervous system. Once the diagnosis of MODS is established, the management is goal-directed to re-establishing end-organ perfusion (such as lungs or kidneys), with resuscitation or supportive therapy [8].

Specific organ failure — There is an early and late cascade of organ failure following a severe burn. The early clinical sequence is characterized by:

●Resuscitation failure

●Inhalation injury

●Acute respiratory distress syndrome

●Hemodynamic failure

●Renal failure

●Liver failure

●Gastrointestinal failure

●Infection

The later clinical sequence is characterized by:

●Pulmonary failure

●Hemodynamic instability

●Renal failure

●Gastrointestinal failure

●Liver failure

Often, multisystem organ failure and death occurs at the end of both cascades. Mortality increases with increasing numbers of failed organ systems. When three or more organ systems have failed, mortality approaches 100 percent [16,17].

Acute tubular necrosis and acute kidney injury — Acute tubular necrosis and acute kidney injury (AKI) are caused by a reduction of cardiac output and blood volume along with an increased secretion of stress mediators (eg, angiotensin, aldosterone, and vasopressin). AKI is associated with a high mortality rate for severely burned adults and children (88 percent and 56 percent, respectively) [18-20]. (See "Definition and staging criteria of acute kidney injury in adults" and "Etiology and diagnosis of prerenal disease and acute tubular necrosis in acute kidney injury in adults".)

Immediate fluid resuscitation upon admission to the emergency department is the fundamental approach to preventing AKI [21]. Early renal failure can occur as a consequence of underperfusion and under-resuscitation. A second period of risk occurs 2 to 14 days after the initial resuscitation [1], and is most likely related to sepsis [22]. In a retrospective review of 238 severely burned patients admitted to an intensive care unit (ICU), AKI occurred in 39 percent, and one in three patients with AKI required renal replacement therapy (RRT) [23]. The percentage of TBSA burned was significantly higher for patients who developed AKI compared with patients without AKI (40.2 versus 25.7 percent TBSA). The mortality rate was significantly higher for patients with AKI compared with patients without AKI (44.1 percent [41 of 93 patients] versus 6.9 percent [10 of 145 patients]). In addition, for patients requiring RRT (n = 32), the mortality rate was higher for patients with early AKI due to under-resuscitation or hypoperfusion compared with patients with late AKI (66.7 versus 57.1 percent).

Management of AKI includes correcting electrolyte abnormalities, volume status (depletion or overload), and metabolic acidosis. Dialysis is performed in the clinical setting when patients are not responsive to these conservative measures. (See "Definition and staging criteria of acute kidney injury in adults" and "Overview of the management of acute kidney injury (AKI) in adults" and "Kidney replacement therapy (dialysis) in acute kidney injury in adults: Indications, timing, and dialysis dose".)

Pulmonary failure — Pulmonary failure is the result of decreased oxygenation, and occurs both initially with the burn injury and within four to eight days after the initial injury due to progression of the inhalation injury and/or fulminant ARDS. The pathophysiology, clinical presentation, and diagnostic evaluation for ARDS are discussed separately. (See "Acute respiratory distress syndrome: Epidemiology, pathophysiology, pathology, and etiology in adults" and "Acute respiratory distress syndrome: Clinical features, diagnosis, and complications in adults".)

Continuous oximetry measurements are critical, as a decrease in oxygen saturation to less than 92 percent is indicative of respiratory failure [1]. Increasing concentrations of inspired oxygen are needed, and when ventilation begins to fail, indicated by growing respiratory rates and hypercarbia, intubation is warranted. (See "Acute respiratory distress syndrome: Fluid management, pharmacotherapy, and supportive care in adults" and "Acute respiratory distress syndrome: Ventilator management strategies for adults" and "Noninvasive ventilation in adults with acute respiratory failure: Benefits and contraindications".)

However, extubation should be performed as soon as possible, since patients can perform their own pulmonary toilet better than through an endotracheal tube or tracheostomy [24,25]. Retrospective studies have suggested that patients treated with a tracheostomy are at risk of tracheostomy site infections and an associated greater risk of pneumonia and death [24,25].

While a tracheostomy is safe, provides a secure airway, and may improve ventilator management, the timing of performing a tracheostomy in patients with burn injury is controversial and should be decided on a patient-by-patient basis, as illustrated by the following examples:

●In a trial of 44 acutely burned adults randomized to early tracheostomy (ET) within the first week or conventional therapy (endotracheal intubation), patients undergoing ET had significant improvement in the ratio of arterial oxygen pressure to inspired oxygen concentration ratio (PaO₂/FiO₂) within 24 hours following the procedure (139±15 versus 190±12 mmHg) [26]. However, patients treated with ET were less likely to undergo extubation on postburn day 14 compared with conventional management (one versus six patients). There were no significant differences in ventilator days, length of stay, incidence of pneumonia, or survival.

●A retrospective review of 38 severely burned children undergoing a tracheostomy within the first week of a severe burn found no statistical difference in pre-tracheostomy oxygenation or ventilation compared with post-tracheostomy ventilation [27]. Peak inspiratory pressures were lower after tracheostomy, accompanied by higher ventilatory volumes and pulmonary compliance, and higher PaO₂/FiO₂ ratios. There were no tracheostomy site infections, tracheostomy-related deaths, or tracheal stenoses in the 30 burn survivors.

Cardiac failure — There are two clinical responses to a severe burn: the ebb and flow states. The ebb state is one of low cardiac output. The flow state is hyperdynamic, in which patients have significantly elevated heart rates and cardiac outputs. These cardiac perturbations occur in nearly all patients with a ≥40 percent TBSA burn. (See "Hypermetabolic response to moderate-to-severe burn injury and management", section on 'Phases'.)

Immediately following a severe burn, patients typically have low cardiac function indices that are characteristic for early shock [28]. At 72 to 96 hours postburn, cardiac output was 150 percent higher than predicted for healthy adults, and remained abnormal at the time of discharge [29]. The heart rate was 160 to 170 percent higher than predicted and remained elevated for up to two years post burn. In addition, myocardial oxygen consumption remained elevated into the rehabilitation phase [30], and increased cardiac stress was associated with myocardial depression [31-33].

In a retrospective review of optimal management of severely burned patients, cardiac stress and myocardial dysfunction may be main contributors to mortality in large burns, implying the therapeutic need to improve cardiac stress and function [34]. Under-resuscitation followed by over-resuscitation leads to pulmonary edema and right heart failure. In infants, right heart failure is a common contributor to burn-related death. Infant hearts may be less compliant, and low filling pressures may plateau stroke volumes, thereby causing the heart to be more sensitive to volume overload [21,35]. (See "Pathophysiology and classification of shock in children", section on 'Cardiogenic shock' and "Definition, classification, etiology, and pathophysiology of shock in adults", section on 'Cardiogenic'.)

To reduce the risk of cardiac failure, judicious fluid resuscitation should be performed upon the patient's arrival to the hospital. For the cardiac dysfunction or hyperdynamic state that occurs in almost all patients with burns >40 percent TBSA, we also use a nonselective beta blocker to block catecholamine receptors [36,37]. (See "Hypermetabolic response to moderate-to-severe burn injury and management", section on 'Propranolol'.)

Hepatic failure — Hepatic failure following a severe burn is generally proportional to the severity of the burn [38]. Immediately following a severe burn and continuing for approximately one week, generalized edema and hepatic hypertrophy occur [39,40]. In a retrospective review of 102 severely burned children, the mean liver size and weight increased during the first week and peaked at two weeks following the burn (mean ± standard error, 85±5 percent and 126±19 percent, respectively) [40]. Twelve months after the burn, the liver remained 50 percent larger than the predicted liver size.

Hepatic protein synthesis is also impaired after a severe burn. As a result of the cellular damage and/or altered membrane permeability, hepatic edema induces an increased release of hepatic enzymes into the circulation. Elevated circulating levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), glutamate dehydrogenase, or alkaline phosphatase (ALKP) are reliable indicators of hepatocyte injury [29,40,41]. However, ALT is a more specific test for hepatocyte injury following a severe burn. Serum levels of the circulating enzymes as high as 200 percent above normal for age have been reported for patients with severe burns.

Serum markers peak early following a severe burn; AST and ALT peak during the first postburn day, and ALKP during the second day, and often normalize prior to discharge. Although these enzymes are elevated as a direct result of the burn injury, additional physiologic processes may be amplifying their expression, including the elevation of ALKP occurring during growth spurts or alongside massive bone resorption. Treatment of acute hepatic failure is supportive, and may include replacement of factors II, VII, IX, and X and albumen until the liver recovers. Management of acute liver failure is discussed separately. Prothrombin time (PT) is a useful marker of hepatic synthetic function, and specifically coagulation. Coupled with the clinical examination, PT can be helpful in the interpretation of other serum liver function tests, especially if abnormal [42]. (See "Acute liver failure in adults: Etiology, clinical manifestations, and diagnosis" and "Acute liver failure in adults: Management and prognosis" and "Acute liver failure in children: Management, complications, and outcomes".)

Hematologic failure — Hematologic failure expressed as a coagulopathy may be caused by depletion and/or impaired synthesis of coagulation factors or by thrombocytopenia. Disseminated intravascular coagulation may be effectively treated by infusion of Fresh Frozen Plasma and cryoprecipitate in order to sustain plasma levels of coagulation factors [1]. (See "Etiology and diagnosis of coagulopathy in trauma patients" and "Evaluation and management of disseminated intravascular coagulation (DIC) in adults".)

Trauma-induced coagulopathy can be present in up to 30 percent of severe trauma victims. This may lead to multisystem organ dysfunction that increases morbidity and mortality. (See 'Multisystem organ dysfunction' above.)

Risk factors for developing hematologic failure or trauma-induced coagulopathy include [21,43,44]:

●Delay in resuscitation

●Under-resuscitation

●Acidosis

●Hypothermia

●Massive blood loss

●High volume transfusion

●Thrombocytopenia

Management is supportive in nature will be based on the etiology of the coagulopathy (eg, warming patient, correcting acidosis, resuscitation). While hematologic failure may occur in the absence of hepatic failure, it is worsened by hepatic failure. Thrombocytopenia with platelet counts lower than 50,000 represents a common finding in severe burn patients and does not require any treatment, except in the clinical setting of diffuse bleeding, when administration of exogenous platelets may be considered [21]. Overall, mortality is high if left untreated, with rates approaching 50 percent [44].

Severely burned patients are at risk for thrombotic and embolic complications, which are likely related to immobilization. Complications of deep venous thrombosis were associated with increasing age, weight, and TBSA burned [43], indicating a need for deep venous thrombosis prophylaxis in the absence of bleeding complications. (See "Overview of the management of the severely burned patient", section on 'Intensive care management'.)

Central nervous system failure — Obtundation is one of the hallmarks of sepsis, and burn patients are no exception. A new onset of mental status changes not attributed to sedative medications in a severely burned patient should incite a search for a septic source [1]. One significant cause of altered mental status in severely burned patients is anoxic brain injury due to hypoperfusion/under-resuscitation or cerebral edema secondary to over-resuscitation. Anoxic brain injury contributes up to 7 percent of fatalities from severe burn injury. Adequate resuscitation in these patients may have been preventative [6,45]. An early cause of acute mental status changes in burn patients is related to inhalation injury and exposure to toxic gases. Carbon monoxide poisoning and cyanide toxicity are common gases responsible for obtunded presentations [46,47].

Neurologic evaluation, including coma syndromes, and management are reviewed elsewhere. (See "Stupor and coma in adults" and "Evaluation of stupor and coma in children".)

Gastrointestinal system failure — Severe burn injury is associated with reduced intestinal blood flow and may also be associated with loss of gut barrier function and enteric bacterial translocation, resulting in a profound hyperinflammatory response leading to gastrointestinal system failure [48,49].

In the clinical setting of low flow states that can occur with inadequate fluid resuscitation following a severe burn, mesenteric blood flow is compromised or inadequate (ie, nonocclusive ischemia), and gut mucosal integrity is compromised. This is best prevented by following goal-directed fluid resuscitation and maintaining optimal hemodynamics. (See "Moderate and severe thermal burns in children: Emergency management", section on 'Fluid resuscitation' and "Emergency care of moderate and severe thermal burns in adults", section on 'Fluid resuscitation' and "Mesenteric venous thrombosis in adults", section on 'Clinical presentations' and "Nonocclusive mesenteric ischemia", section on 'Clinical features' and "Overview of intestinal ischemia in adults", section on 'Clinical features'.)

Gut mucosal atrophy occurs in the absence of intraluminal feeds and is another cause of gastrointestinal failure after severe burn injury [50,51]. Early enteral nutrition, started 24 to 48 hours after burn injury, is one of the only therapies shown to decrease this complication. Early enteral nutrition is well tolerated after severe burn injury [52,53]. (See "Overview of nutrition support in burn patients" and "Clinical assessment and monitoring of nutrition support in adult surgical patients" and "Nutritional demands and enteral formulas for adult surgical patients".)

There are some data to support the contention that enteral feedings have beneficial effects on outcome in injured patients when compared with parenteral feedings, possibly via an enhancement of gastrointestinal barrier integrity [54]. However, these data require confirmation prior to general application.

BURN-SPECIFIC COMPLICATIONS

Burn wound infection and sepsis — Infection is a common cause of morbidity and mortality in burn patients. Any rapid change in the burn wound appearance or the clinical condition of the burn patient may herald burn wound infection or sepsis. The different categories of burn wound infection are based on clinical features and depth of invasion, which is determined through cultures and histopathology of tissue obtained by burn wound biopsy. Specific criteria that include the presence of microbial invasion into adjacent normal tissue, among other criteria, have been suggested by the American Burn Association (ABA) to define burn wound sepsis. The clinical features, criteria for, and management of burn wound infection and sepsis are discussed in detail elsewhere. (See "Burn wound infection and sepsis".)

Ongoing hypermetabolism — A prolonged hypermetabolic, proinflammatory, catabolic state is characteristic of severe burns. Partial-thickness and/or full-thickness burns covering more than 40 percent total body surface area (TBSA) are associated with a significant stress response, inflammation, and severe hypermetabolism, resulting in hyperdynamic circulation, augmented body temperature regulation, proteolysis, glycolysis, lipolysis, and inefficient substrate cycling [2,55-60]. Enhanced catecholamine, glucocorticoid, glucagon, and dopamine secretion account for the initiation of the acute hypermetabolic response and the associated catabolic state [55,61-67]. Release of insulin is increased in response to glucose load when compared with controls [68,69] and glucose levels remain elevated, indicating an insulin-resistant state [69,70]. The hypermetabolic response can persist for three years following a severe burn [55,61,67,71-73]. (See "Hypermetabolic response to moderate-to-severe burn injury and management".)

Hypertrophic scarring and keloid formation — Keloid formation and hypertrophic scarring are unfortunately quite common following burn injury. These are discussed in detail separately. (See "Keloids and hypertrophic scars" and "Hypertrophic scarring and keloids following burn injuries".)

Heterotopic ossification — Heterotopic ossification is not simply calcification of tissue, but is the formation of lamellar bone in an abnormal location (eg, joint) after a prolonged inflammatory state [74-76]. It is hypothesized to result from the presence of osteoprogenitor cells induced by the proinflammatory inciting event [74,77,78], but the precise mechanism of heterotopic ossification remains unknown [74-76]. It is primarily associated with traumatic brain injury, spinal cord injury, trauma, burns, surgery, and prolonged periods of immobilization. (See "Surgical management of severe lower extremity injury", section on 'Heterotopic ossification'.)

The reported incidence of heterotopic ossification formation in the burn population is between 0.1 and 20 percent depending upon the size of the burn and the cohort of burn patients studied [74-76]. It has been observed in patients as early as 30 days post-injury [74-76]. It has been reported to occur in all major joints, but is most commonly reported in the elbow or knees [74-76]. Early burn wound excision and grafting may mitigate the hypermetabolic response and inflammatory response, thus seeming to reduce the incidence. However, prolonged periods of immobility, either before or after grafting, are also considered a risk factor [74-76].

Once heterotopic ossification has formed, it causes significant morbidity by decreasing range of motion and causing neuropathy, weakness, pain, and stiffness, which increase the length of stay and hospital costs. Specifically, patients will often complain of their joints "locking" [74]. The first signs are often simply the decreased range of motion, pain, and swelling noted by patients and/or physiotherapy that are nonspecific. The pathologic bone formation may be seen on plain film [74-76]. Treatment includes ongoing intensive physiotherapy, possibly nonsteroidal anti-inflammatory drugs (NSAIDs), investigational drugs (eg, bisphosphonates), and early surgical excision of the heterotopic bone [74-76]. Prevention is focused on early mobilization (passive or active).

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Care of the patient with burn injury".)

SUMMARY

●Multiple organ dysfunction syndrome (MODS) is a progressive disorder that commonly occurs in acutely ill patients and exists in a continuum with the systemic inflammatory response syndrome (SIRS) which affects most patients with a severe burn, with or without an infection. The risk of MODS increases with burn wounds >20 percent TBSA, increasing age, male sex, sepsis, hypoperfusion, and under-resuscitation. (See 'Multisystem organ dysfunction' above.)

●Immediate fluid resuscitation upon admission to the emergency department is the fundamental approach to preventing acute kidney injury. Early renal failure can occur as a consequence of underperfusion and under-resuscitation. A second period of risk occurs 2 to 14 days after the initial resuscitation and is most likely related to sepsis. (See 'Acute tubular necrosis and acute kidney injury' above.)

●Gut mucosal atrophy occurs in the absence of intraluminal feeds and is another cause of gastrointestinal failure after severe burn injury. Early enteral nutrition, started 24 to 48 hours after burn injury, is one of the only therapies shown to decrease this complication. (See 'Gastrointestinal system failure' above and "Overview of nutrition support in burn patients".)

●Depression and post-traumatic stress disorder (PTSD) are the most common psychologic problems, occurring in 13 to 23 percent and 13 to 45 percent of patients, respectively. (See "Overview of the management of the severely burned patient", section on 'Psychological aspects'.)